| First Author | Antoni A | Year | 2011 |
| Journal | Immunogenetics | Volume | 63 |
| Issue | 5 | Pages | 291-308 |
| PubMed ID | 21229240 | Mgi Jnum | J:192148 |
| Mgi Id | MGI:5464088 | Doi | 10.1007/s00251-010-0507-3 |
| Citation | Antoni A, et al. (2011) Macrophages from lupus-prone MRL mice have a conditional signaling abnormality that leads to dysregulated expression of numerous genes. Immunogenetics 63(5):291-308 |
| abstractText | Macrophages (mvarphi) from pre-diseased mice of the major murine inbred models of spontaneous autoimmunity (AI), including multiple lupus-prone strains and the type I diabetes-prone NOD (non-obese diabetic) strain, have identical apoptotic target-dependent abnormalities. This characteristic feature of mvarphi from AI-prone mice suggests that abnormal signaling events induced within mvarphi following their interaction with apoptotic targets may predispose to AI. Such signaling abnormalities would affect predominantly the processing and presentation of self-antigen (i.e., derived from apoptotic targets), while sparing the processing and presentation of foreign antigen (i.e., derived from non-apoptotic sources). Here, we used DNA microarrays to test the hypothesis that mvarphi from AI-prone mice (MRL/MpJ [MRL/+] or MRL/MpJ-Tnfrsf6 ( lpr ) [MRL/lpr]) differentially express multiple genes in comparison to non-AI mvarphi (BALB/c), but do so in a largely apoptotic cell-dependent manner. Mvarphi were stimulated with lipopolysaccharide, a potent innate stimulus, in the presence or absence of serum (an experimental surrogate for apoptotic targets). In accord with our hypothesis, the number of genes differentially expressed by MRL mvarphi was significantly increased in the presence vs. the absence of serum, the apoptotic target surrogate (n = 401 vs. n = 201). Notably, for genes differentially expressed by MRL mvarphi in the presence of serum, serum-free culture normalized their expression to a level statistically indistinguishable from that by non-AI mvarphi. Comparisons of mvarphi from AI-prone NOD and non-AI C57BL/6 mice corroborated these findings. Together, these data support the hypothesis that mvarphi from MRL and other AI-prone mice are characterized by a conditional abnormality elicited by serum lipids or apoptotic targets. |
